Researchers have found a new target that could lead to better therapies to prevent bone fractures for type 2 diabetes patients.
A team from New York University has discovered that hyperglycemic mice have a 24-fold higher accumulation of succinate—an intermediate metabolite—in the metabolic pathways of their bone marrow stromal cells, while succinate was barely detectable in normal mice.
“The results are important because diabetics have a significantly higher fracture risk and their healing process is always delayed,” Xin Li, PhD, associate professor of basic science and craniofacial biology at NYU Dentistry, and the study’s senior investigator, said in a statement. “In our study, the hyperglycemic mice had increased bone resorption [the breakdown and absorption of old bone], which outpaced the formation of new bone.
“This has implications for bone protection, as well as for the treatment of diabetes-associated collateral bone damage.”
During the study the researchers took samples of bone marrow from hyperglycemic male mice and healthy mice and studied the bone metabolism at the cellular level using advanced imaging and computational techniques. They identified 142 metabolites that were significantly altered by more than 1.5 times in the diabetic mice, 126 of which were increased while 16 were decreased.
Succinate is the first metabolite in the energy pathway and with its more than 20-fold increased concentration, it overwhelmed the energy pathways. The diabetic mice also had a considerably lower spongy bone mass called trabecular bone, making it easier to fracture.
“The bottom line is that the high level of succinate combined with the finding of more fragile bone points to a new target to protect bone,” Dr. Yuqi Guo, an associate research scientist at NYU Dentistry and the study’s first author, said in a statement.
The researchers utilized metabolomics to examine the small molecules within cells, bio-fluids, tissue or organisms and their interactions within the larger system.
According to the U.S Centers for Disease Control and Prevention data from 2012, diabetes affects 29.1 million Americans. The Women’s Health Initiative also found that type 2 diabetes was linked to a 20 percent increase in fractures.
